Clinical Trials

Patients are invited to participate in a research study of liver perfusion (how blood flows
to the liver over time). Researchers hope to learn whether perfusion characteristics of
liver metastases may be predictive of response to treatment and whether liver perfusion
characteristics can be used to follow response to treatment. Patients were selected as a
possible participant in this study because they are identified as having liver metastases

This pilot clinical trial studies how well photoacoustic imaging works in detecting ovarian
or fallopian tube cancer. Photoacoustic imaging is an imaging method that uses lasers to
light up tissue, and then converts the light information into ultrasound images.
Photoacoustic imaging can provide images of the structure of tissues, as well as their
function and the levels of molecules, such as the flow of blood in blood vessels and the
level of oxygen in the blood. Photoacoustic imaging may help doctors determine whether a
mass is benign (non-cancerous) or cancerous based on the molecular differences between
cancer and normal tissue. It may be more accurate and less expensive than other imaging
methods, and does not expose patients to radiation.

Fluorine-18 Fluorodeoxyglucose (F-18 FDG) PET/CT is established as a powerful imaging tool
for cancer detection and monitoring response to therapy. Sodium Fluorine-18 (F-18) was used
in the 1970s for bone scanning and can be used as a skeletal tracer in current PET/CT
scanners. The combined administration of F-18 and F-18 FDG in a single PET/CT scan for
cancer detection was not attempted to date. We hope to learn what is the best approach for
detection of cancer and thus to improve cancer treatment.

Abstract

Continuous improvements in magnetic resonance scanner, coil, and pulse sequence technology have resulted in the ability to perform routine, high-quality imaging of the brachial plexus. With knowledge of the anatomy of the plexus, and a familiarity with common pathologic conditions affecting this area, radiologists can provide valuable imaging evaluation of patients with brachial plexus pathologies.

Abstract

Early detection of pancreatic ductal adenocarcinoma (PDAC) allows for surgical resection and increases patient survival times. Imaging agents that bind and amplify the signal of neovascular proteins in neoplasms can be detected by ultrasound, enabling accurate detection of small lesions. We searched for new markers of neovasculature in PDAC and assessed their potential for tumor detection by ultrasound molecular imaging.Thymocyte Differentiation Antigen 1 (Thy1) was identified as a specific biomarker of PDAC neovasculature by proteomic analysis. Upregulation in PDAC was validated by immunohistochemical analysis of pancreatic tissue samples from 28 healthy individuals, 15 with primary chronic pancreatitis tissues, and 196 with PDAC. Binding of Thy1-targeted contrast microbubbles was assessed in cultured cells, in mice with orthotopic PDAC xenograft tumors expressing human Thy1 on the neovasculature, and on the neovasculature of a genetic mouse model of PDAC.Based on immunohistochemical analyses, levels of Thy1 were significantly higher in the vascular of human PDAC than chronic pancreatitis (P=.007) or normal tissue samples (P

Abstract

To assess early treatment effects on computed tomography (CT) perfusion parameters after antiangiogenic and radiation therapy in subcutaneously implanted, human colon cancer xenografts in mice and to correlate in vivo CT perfusion parameters with ex vivo assays of tumor vascularity and hypoxia.Dynamic contrast-enhanced CT (perfusion CT, 129 mAs, 80 kV, 12 slices × 2.4 mm; 150 ?L iodinated contrast agent injected at a rate of 1 mL/min intravenously) was performed in 100 subcutaneous human colon cancer xenografts on baseline day 0. Mice in group 1 (n=32) received a single dose of the antiangiogenic agent bevacizumab (10 mg/kg body weight), mice in group 2 (n=32) underwent a single radiation treatment (12 Gy), and mice in group 3 (n=32) remained untreated. On days 1, 3, 5, and 7 after treatment, 8 mice from each group underwent a second CT perfusion scan, respectively, after which tumors were excised for ex vivo analysis. Four mice were killed after baseline scanning on day 0 for ex vivo analysis. Blood flow (BF), blood volume (BV), and flow extraction product were calculated using the left ventricle as an arterial input function. Correlation of in vivo CT perfusion parameters with ex vivo microvessel density and extent of tumor hypoxia were assessed by immunofluorescence. Reproducibility of CT perfusion parameter measurements was calculated in an additional 8 tumor-bearing mice scanned twice within 5 hours with the same CT perfusion imaging protocol.The intraclass correlation coefficients for BF, BV, and flow extraction product from repeated CT perfusion scans were 0.93 (95% confidence interval: 0.78, 0.97), 0.88 (0.66, 0.95), and 0.88 (0.56, 0.95), respectively. Changes in perfusion parameters and tumor volumes over time were different between treatments. After bevacizumab treatment, all 3 perfusion parameters significantly decreased from day 1 (P ? 0.006) and remained significantly decreased until day 7 (P ? 0.008); tumor volume increased significantly only on day 7 (P=0.04). After radiation treatment, all 3 perfusion parameters decreased significantly on day 1 (P < 0.001); BF and flow extraction product increased again on day 3 and 5, although without reaching statistically significant difference; and tumor volumes did not change significantly at all time points (P ? 0.3). In the control group, all 3 perfusion parameters did not change significantly, whereas tumor volume increased significantly at all the time points, compared with baseline (P ? 0.04). Ex vivo immunofluorescent staining showed good correlation between all 3 perfusion parameters and microvessel density (?=0.71, 0.66, and 0.69 for BF, BV, and flow extraction product, respectively; P < 0.001). There was a trend toward negative correlation between extent of hypoxia and all 3 perfusion parameters (?=-0.53, -0.47, and -0.40 for BF, BV, and flow extraction product, respectively; P ? 0.05).CT perfusion allows a reproducible, noninvasive assessment of tumor vascularity in human colon cancer xenografts in mice. After antiangiogenic and radiation therapy, BF, BV, and flow extraction product significantly decrease and change faster than the tumor volume.

Abstract

To evaluate ultrasonography (US) by using contrast agent microbubbles (MBs) targeted to P-selectin (MB(P-selectin)) to quantify P-selectin expression levels in inflamed tissue and to monitor response to therapy in a murine model of chemically induced inflammatory bowel disease (IBD).All procedures in which laboratory animals were used were approved by the institutional administrative panel on laboratory animal care. Binding affinity and specificity of MB(P-selectin) were tested in cell culture experiments under flow shear stress conditions and compared with control MBs (MB(Control)). In vivo binding specificity of MB(P-selectin) to P-selectin was tested in mice with trinitrobenzenesulfonic acid-induced colitis (n = 22) and control mice (n = 10). Monitoring of anti-tumor necrosis factor ? antibody therapy was performed over 5 days in an additional 30 mice with colitis by using P-selectin-targeted US imaging, by measuring bowel wall thickness and perfusion, and by using a clinical disease activity index score. In vivo targeted contrast material-enhanced US signal was quantitatively correlated with ex vivo expression levels of P-selectin as assessed by quantitative immunofluorescence.Attachment of MB(P-selectin) to endothelial cells was significantly (P = .0001) higher than attachment of MB(Control) and significantly (? = 0.83, P = .04) correlated with expression levels of P-selectin on endothelial cells. In vivo US signal in mice with colitis was significantly higher (P = .0001) with MB(P-selectin) than with MB(Control). In treated mice, in vivo US signal decreased significantly (P = .0001) compared with that in nontreated mice and correlated well with ex vivo P-selectin expression levels (? = 0.69; P = .04). Colonic wall thickness (P ? .06), bowel wall perfusion (P ? .85), and clinical disease activity scoring (P ? .06) were not significantly different between treated and nontreated mice at any time.Targeted contrast-enhanced US imaging enables noninvasive in vivo quantification and monitoring of P-selectin expression in inflammation in murine IBD.

Abstract

Ovarian cancer is the most lethal of the gynecologic malignancies. Because ovarian cancer symptoms are subtle and nonspecific, the diagnosis is often delayed until the disease is well advanced. Overall 5-year survival is a rather dismal 50% but can be improved to greater than 90% if the disease is confined to the ovary at the time of diagnosis (generally in fewer than 25% of patients). Effective screening tools are currently not available. Owing to the rather low incidence of the disease in the general population, potential screening tests must provide very high specificity to avoid unnecessary interventions in false-positive cases. This article reviews currently available serum biomarkers and imaging tests for the early detection of ovarian cancer and provides an outlook on the potential improvements in these noninvasive diagnostic tools that may lead to successful implementation in a screening program. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11090563/-/DC1.

Abstract

Targeted contrast-enhanced ultrasound imaging is increasingly being recognized as a powerful imaging tool for the detection and quantification of tumor angiogenesis at the molecular level. The purpose of this study was to develop and test a new class of targeting ligands for targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with small, conformationally constrained peptides that can be coupled to the surface of ultrasound contrast agents.Directed evolution was used to engineer a small, disulfide-constrained cystine knot (knottin) peptide that bound to alpha(v)beta(3) integrins with a low nanomolar affinity (Knottin(Integrin)). A targeted contrast-enhanced ultrasound imaging contrast agent was created by attaching Knottin(Integrin) to the shell of perfluorocarbon-filled microbubbles (MB-Knottin(Integrin)). A knottin peptide with a scrambled sequence was used to create control microbubbles (MB-Knottin(Scrambled)). The binding of MB-Knottin(Integrin) and MB-Knottin(Scrambled) to alpha(v)beta(3) integrin-positive cells and control cells was assessed in cell culture binding experiments and compared with that of microbubbles coupled to an anti-alpha(v)beta(3) integrin monoclonal antibody (MB(alphavbeta3)) and microbubbles coupled to the peptidomimetic agent c(RGDfK) (MB(cRGD)). The in vivo imaging signals of contrast-enhanced ultrasound with the different types of microbubbles were quantified in 42 mice bearing human ovarian adenocarcinoma xenograft tumors by use of a high-resolution 40-MHz ultrasound system.MB-Knottin(Integrin) attached significantly more to alpha(v)beta(3) integrin-positive cells (1.76 +/- 0.49 [mean +/- SD] microbubbles per cell) than to control cells (0.07 +/- 0.006). Control MB-Knottin(Scrambled) adhered less to alpha(v)beta(3) integrin-positive cells (0.15 +/- 0.12) than MB-Knottin(Integrin). After blocking of integrins, the attachment of MB-Knottin(Integrin) to alpha(v)beta(3) integrin-positive cells decreased significantly. The in vivo ultrasound imaging signal was significantly higher after the administration of MB-Knottin(Integrin) than after the administration of MB(alphavbeta3) or control MB-Knottin(Scrambled). After in vivo blocking of integrin receptors, the imaging signal after the administration of MB-Knottin(Integrin) decreased significantly (by 64%). The imaging signals after the administration of MB-Knottin(Integrin) were not significantly different in the groups of tumor-bearing mice imaged with MB-Knottin(Integrin) and with MB(cRGD). Ex vivo immunofluorescence confirmed integrin expression on endothelial cells of human ovarian adenocarcinoma xenograft tumors.Integrin-binding knottin peptides can be conjugated to the surface of microbubbles and used for in vivo targeted contrast-enhanced ultrasound imaging of tumor angiogenesis. Our results demonstrate that microbubbles conjugated to small peptide-targeting ligands provide imaging signals higher than those provided by a large antibody molecule.

Abstract

To retrospectively compare, in a multiobserver study, double-contrast-material (sequential administration of ferucarbotran and gadobutrol) magnetic resonance (MR) imaging with single-contrast-material ferucarbotran-enhanced and dynamic postferucarbotran gadobutrol-enhanced MR imaging for the detection and characterization of benign and malignant focal liver lesions.This study was institutional review board approved, and the requirement for informed patient consent was waived. Eighty-nine patients with a total of 128 focal liver lesions underwent double-contrast liver MR imaging (nonenhanced, ferucarbotran-enhanced, and dynamic postferucarbotran gadobutrol-enhanced MR imaging performed during one session). Four readers independently reviewed the data sets during three reading sessions focused on focal liver lesion detection and characterization: In session 1, the nonenhanced and dynamic postferucarbotran gadobutrol-enhanced images obtained at double-contrast MR imaging were analyzed. In session 2, the nonenhanced and ferucarbotran-enhanced images were analyzed. In session 3, all MR images were analyzed together. The diagnostic performance of each MR technique and each reader was evaluated by using receiver operating characteristic (ROC) analysis; differences between postferucarbotran gadobutrol-enhanced, ferucarbotran-enhanced, and double-contrast MR imaging were assessed at Wilcoxon signed rank testing; and interreader agreement was assessed at Cohen kappa analysis. Histopathologic confirmation or an unchanged clinical course or MR finding was the reference standard.The four readers' detection of the benign and malignant lesions was not significantly different (P > or = .11) between the three MR techniques. The benign and malignant focal liver lesions were differentiated with significantly higher confidence (P < or = .01) on the double-contrast (area under ROC curve [A(z)] = 0.988) and ferucarbotran-enhanced (A(z) = 0.985) MR images than on the dynamic gadobutrol-enhanced images (A(z) = 0.963). Accuracy in the diagnosis of hepatocellular carcinoma (HCC) was highest (P = .02) and confidence in the final diagnosis of HCC (P = .001) or metastasis (P = .049) was significantly higher with double-contrast imaging.In select cases, double-contrast MR imaging can improve diagnostic accuracy and increase confidence in characterizing focal liver lesions as HCC or metastasis.

Abstract

The purpose of the study was to retrospectively compare three-dimensional gadolinium-enhanced magnetic resonance angiography (conventional MRA) with MRA accelerated by a parallel acquisition technique (fast MRA) for the assessment of visceral arteries, using 64-detector-row computed tomography angiography (MDCTA) as the reference standard. Eighteen patients underwent fast MRA (imaging time 17 s), conventional MRA (29 s) and MDCTA of the abdomen and pelvis. Two independent readers assessed subjective image quality and the presence of arterial stenosis. Data were analysed on per-patient and per-segment bases. Fast MRA yielded better subjective image quality in all segments compared with conventional MRA (P = 0.012 for reader 1, P = 0.055 for reader 2) because of fewer motion-induced artefacts. Sensitivity and specificity of fast MRA for the detection of arterial stenosis were 100% for both readers. Sensitivity of conventional MRA was 89% for both readers, and specificity was 100% (reader 1) and 99% (reader 2). Differences in sensitivity between the two types of MRA were not significant for either reader. Interobserver agreement for the detection of arterial stenosis was excellent for fast (kappa = 1.00) and good for conventional MRA (kappa = 0.76). Thus, subjective image quality of visceral arteries remains good on fast MRA compared with conventional MRA, and the two techniques do not differ substantially in the grading of arterial stenosis, despite the markedly reduced acquisition time of fast MRA.

Abstract

The aim of this study was to compare signal characteristics of the synovium in knees of asymptomatic volunteers before and after intravenous administration of ultrasmall superparamagnetic iron oxide particles (USPIO). Ten knees of 10 asymptomatic volunteers were examined before and 36 h after intravenous administration of USPIO on a 1.5-T MR system using T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo (GRE), and short inversion time inversion-recovery sequences. In addition, synovial perfusion was measured using Gd-enhanced GRE imaging during the first imaging session. Images were analyzed qualitatively for any visual changes before and after USPIO administration. Signal-to-noise ratios (SNR) of the synovium were determined on unenhanced and USPIO-enhanced sequences. All MR images were reviewed for presence of any degenerative changes. Qualitative image analysis revealed no visually detectable changes of any knee joint before and after USPIO administration. The SNR values of the synovium on T1w, T2w, and T2*w images before and after USPIO administration showed no significant difference (T1, P = 0.86; T2, P = 0.95; T2*, P = 0.86). None of the volunteers showed any relevant degenerative changes of the knee and synovial perfusion was within normal limits. In knees of asymptomatic volunteers without any relevant degenerative changes and normal synovial perfusion neither visual changes nor changes of SNR values of the synovium can be depicted after USPIO administration. This means that USPIO-enhanced MRI may be used for assessment of knee disorders with increased macrophage activity.

Abstract

To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs.Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.

Abstract

Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm(3) and 3,610.14 mm(3) for CA125 and between 0.21 mm(3) and 131.51 mm(3) for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm(3) and 1.52 x 10(6) mm(3) for CA125 and between 27 mm(3) and 3.45 x 10(5) mm(3) for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.This study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable tumor sizes for novel proteomic biomarker assays if sufficient physiologic data for the biomarker are available. The model may address the potential and limitations of tumor biomarkers, help prioritize biomarkers, and guide investments into early cancer detection research efforts.

Abstract

To retrospectively evaluate the performance of breath-hold contrast-enhanced 3D dynamic parallel gradient echo MRI (pMRT) for the characterization of focal liver lesions (standard of reference: histology) and for the analysis of hepatic vasculature (standard of reference: contrast-enhanced 64-detector row computed tomography; MSCT) in a single MRI session.Two blinded readers independently analyzed preoperative pMRT data sets (1.5T-MRT) of 45 patients (23 men, 22 women; 28 - 77 years, average age, 48 years) with a total of 68 focal liver lesions with regard to image quality of hepatic arteries, portal and hepatic veins, presence of variant anatomy of the hepatic vasculature, as well as presence of portal vein thrombosis and hemodynamically significant arterial stenosis. In addition, both readers were asked to identify and characterize focal liver lesions. Imaging parameters of pMRT were: TR/TE/matrix/slice thickness/acquisition time: 3.1 ms/ 1.4 ms/ 384 x 224 / 4 mm/ 15 - 17 s. MSCT was performed with a pitch of 1.2, an effective slice thickness of 1 mm and a matrix of 512 x 512.Based on histology, the 68 liver lesions were found to be 42 hepatocellular carcinomas (HCC), 20 metastases, 3 cholangiocellular carcinomas (CCC) as well as 1 dysplastic nodule, 1 focal nodular hyperplasia (FNH) and 1 atypical hemangioma. Overall, the diagnostic accuracy was high for both readers (91 - 100 %) in the characterization of these focal liver lesions with an excellent interobserver agreement (kappa-values of 0.89 [metastases], 0.97 [HCC] and 1 [CCC]). On average, the image quality of all vessels under consideration was rated good or excellent in 89 % (reader 1) and 90 % (reader 2). Anatomical variants of the hepatic arteries, hepatic veins and portal vein as well as thrombosis of the portal vein were reliably detected by pMRT. Significant arterial stenosis was found with a sensitivity between 86 % and 100 % and an excellent interobserver agreement (kappa = 0.85).Diagnostic image quality remains good or excellent in most cases when the data acquisition time is accelerated by means of parallel imaging in dynamic MRI. It allows reliable detection and characterization of focal liver lesions as well as the depiction of hepatic vascular variants, portal vein thrombosis, and arterial stenosis. Introducing pMRT in routine liver MRI may be another step towards a simplified diagnostic work-up prior to liver surgery.

Abstract

The study was approved by the institutional review board, and informed consent was obtained from all patients. The purpose of this study was to retrospectively evaluate the feasibility, reliability, and accuracy of breath-hold dynamic contrast material-enhanced parallel gradient-echo (GRE) magnetic resonance (MR) imaging for mapping the hepatic vascular anatomy, with contrast-enhanced 64-detector row computed tomography (CT) as the reference standard. The parallel GRE MR data sets of 100 patients acquired at 1.5 T were evaluated independently by two blinded readers with respect to (a) image quality for depiction of the hepatic arteries and the portal and hepatic veins and (b) presence of arterial stenosis and variant hepatic vasculature. The readers rated image quality to be good or excellent for 91.1%-100% of the vessels. At parallel GRE MR imaging, the readers diagnosed variant hepatic vessels and arterial stenosis with 94%-100% accuracy. They concluded that parallel GRE MR imaging, as compared with 64-detector row CT, is feasible for hepatic vascular mapping and enables reliable and accurate detection of variant hepatic vasculature and diagnosis of arterial stenosis. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2453062103/DC1.

Abstract

To prospectively compare the image quality, sensitivity, and specificity of three-dimensional gadolinium-enhanced magnetic resonance (MR) angiography accelerated by parallel acquisition (ie, fast MR angiography) with MR angiography not accelerated by parallel acquisition (ie, conventional MR angiography) for assessment of aortoiliac and renal arteries, with digital subtraction angiography (DSA) as the reference standard.The study was approved by the institutional review board; informed consent was obtained from all patients. Forty consecutive patients (33 men, seven women; mean age, 63 years) suspected of having aortoiliac and renal arterial stenoses and thus examined with DSA underwent both fast (mean imaging time, 17 seconds) and conventional (mean imaging time, 29 seconds) MR angiography. The arterial tree was divided into segments for image analysis. Two readers independently evaluated all MR angiograms for image quality, presence of arterial stenosis, and renal arterial variants. Image quality, sensitivity, and specificity were analyzed on per-patient and per-segment bases for multiple comparisons (with Bonferroni correction) and for dependencies between segments (with patient as the primary sample unit). Interobserver agreement was evaluated by using kappa statistics.Overall, the image quality with fast MR angiography was significantly better (P=.001) than that with conventional MR angiography. At per-segment analysis, the image quality of fast MR angiograms of the distal renal artery tended to be better than that of conventional MR angiograms of these vessels. Differences in sensitivity for the detection of arterial stenosis between the two MR angiography techniques were not significant for either reader. Interobserver agreement in the detection of variant renal artery anatomy was excellent with both conventional and fast MR angiography (kappa=1.00).Fast MR angiography and conventional MR angiography do not differ significantly in terms of arterial stenosis grading or renal arterial variant detection.

Abstract

To evaluate 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) accumulation in human ovarian carcinoma cell lines compared with control tumor cell lines known to accumulate FDG.FDG accumulation assays were performed in 15 different ovarian carcinoma cell lines at 1, 2, and 3 hours after incubation with 1 microCi of FDG. Results were compared with FDG accumulation in six different control tumor cell lines. 2-deoxy-2-[F-18]fluoro-D-glucose accumulation was expressed as counts per minute (cpm) in cells and normalized to initial cpm in medium and total protein content of cell lysates.FDG accumulation in all 15 ovarian carcinoma cell lines was equal to or higher than 0.0005 +/- 8.6 10(-5) cpm in cells/cpm in medium/mug protein at all three different time points. In two ovarian carcinoma cell lines (ES-2, poorly differentiated clear cell carcinoma, and OVCAR-3, poorly differentiated papillary adenocarcinoma), FDG accumulation was not statistically, significantly different compared to the control cell line with the highest FDG accumulation (LS 174T human colorectal adenocarcinoma) at two or more time points (P > or = 0.07). In 2 of 15 (13%) ovarian carcinoma cell lines (OVCAR5 epithelial carcinoma and SKOV3 clear cell carcinoma), FDG accumulation was lower than that in the control cell line with the lowest FDG accumulation (HT-29 human colorectal adenocarcinoma) at one or more time points (P < 0.05).Most human ovarian carcinoma cell lines showed comparable FDG accumulations with control cell lines known to accumulate FDG. This study lays the foundations for further comparisons with other ovarian cancer cell lines and for other positron emission tomography tracers.

Abstract

The purpose of this study was to evaluate a new three-dimensional gradient-echo (GRE) MR sequence performed with a parallel acquisition technique to shorten breath-hold times (parallel GRE MRI) in the detection of arterial variants and stenosis of the abdominal aorta and its visceral branches. A total of 102 patients underwent dynamic parallel GRE MRI, timed to the arterial phase by a test bolus (mean breath-hold time, 17 s). For both quantitative and qualitative analysis, the abdominal aorta and its visceral branches were divided into 13 arterial segments. In a subanalysis of 55/102 patients, the accuracy of parallel GRE MRI compared to MDCT in the detection arterial variants and stenosis was calculated for two independent readers. Mean SNRs and CNRs were 47.2 and 35.6, respectively. Image quality was rated good or excellent in 1,234/1,326 segments (93%). Hepatic and renal arterial variants were identified with an accuracy of 93 and 95%, respectively (reader 1) and 98 and 100%, respectively (reader 2). Both readers detected arterial stenosis with an accuracy of 98%. Interobserver agreement was good to excellent for the detection of hepatic (kappa=0.69) and renal (kappa=0.92) variants and for the diagnosis of stenosis (kappa=0.96). Dynamic three-dimensional parallel GRE MRI is feasible and allows a reliable and accurate diagnosis of arterial variants and stenosis of the abdominal aorta and its visceral branches in a short breath-hold-time.

Abstract

The purpose of this study was to compare respiratory-triggered balanced steady-state free precession (bSSFP) with breath-hold contrast-enhanced dynamic two-dimensional (2D) gradient-echo (GRE) and time-of-flight (TOF) magnetic resonance imaging (MRI) for portal and hepatic vein visualization and assessment of portal and hepatic venous variants. Sixty patients with liver disease underwent nonenhanced bSSFP and contrast-enhanced GRE, bSSFP, and TOF imaging. Contrast-to-noise ratios (CNRs) for portal and hepatic veins were measured. Two readers rated the quality of portal and hepatic vein visualization on a 5-point Likert scale. The diagnostic performance of each MRI series in the detection of portal and hepatic venous variants was assessed in 40/60 patients who also underwent contrast-enhanced multidetector-row computed tomography (MDCT). CNRs for portal and hepatic veins were highest on contrast-enhanced bSSFP images. Image quality of portal and hepatic veins was rated higher for nonenhanced bSSFP than for contrast-enhanced GRE (p<0.03) and TOF (p<0.003) and higher for contrast-enhanced than for nonenhanced bSSFP (p<0.003). Compared with MDCT, portal and hepatic venous variants were identified with an accuracy of 99% on bSSFP images, with an excellent interobserver agreement (kappa=0.97). Compared with MDCT, presence of surgically important portal and hepatic venous anatomical variants can be predicted with high accuracy on bSSFP images.

Abstract

To evaluate whether ultrasmall superparamagnetic iron particles (USPIO)-enhanced MRI is capable of assessing both synovial perfusion characteristics and the presence of synovial macrophages in a model of antigen-induced arthritis.Unilateral arthritis was induced in six knees of six rabbits. The contralateral knees of the rabbits served as control knees. After onset of arthritis, all 12 knees were scanned prior to and immediately following intravenous administration of USPIO using a multiphase T1-weighted (T1w) fast gradient-echo (FGRE) sequence, and T1w spin-echo (SE), T2-weighted (T2w) FSE, T2*w GRE, and short-tau inversion recovery (STIR) sequences prior to and 24 hours following USPIO administration. SI-vs.-time curves (STCs) and the early enhancement rate during the first 56 seconds (REE(56)) were calculated from SI measurements within the synovial tissue of all knees on dynamic T1w images. MR findings were correlated to histopathology.REE(56) was significantly higher in the synovial tissue of arthritic knees than in the control knees (P < 0.01). Significant T1-, T2-, and T2* effects (P = 0.03-0.04) and multiple synovial vessels were visually detectable within the arthritic synovial tissue 24 hours after administration of USPIO, whereas no signal changes or synovial vessels were seen in the control knees. Histopathology revealed widened synovial blood vessels in the arthritic knees, and confirmed iron uptake by macrophages in the arthritic knees.USPIO-enhanced MRI is capable of both assessing synovial hyperperfusion and detecting macrophages in antigen-induced arthritis in rabbits.

Abstract

To describe dose-dependent signal intensity (SI) characteristics of experimentally induced soft-tissue abscesses on 1.5-T T1- and T2*-weighted magnetic resonance (MR) images obtained 24 hours after administration of ultrasmall superparamagnetic iron oxide (USPIO) and to describe the relationship between SI and amount of USPIO uptake and macrophage iron content.Local institutional review committee on animal care approved the experiments, which were performed according to the guidelines of the National Institutes of Health and the committee on animal research at our institution. Unilateral calf muscle abscesses were induced in 21 rats with an injection of a Staphylococcus aureus suspension. The rats were divided into three groups of seven animals each: low USPIO dose (50 micromol of iron per kilogram of body weight), high USPIO dose (150 micromol Fe/kg), and control (saline solution). All rats were imaged before and 24 hours after USPIO administration at 1.5 T (transverse T1-weighted spin-echo, T2*-weighted fast gradient-echo, and short inversion time inversion-recovery sequences). Images were analyzed quantitatively and qualitatively with regard to SI and signal pattern. Temporal variation of calculated contrast-to-noise ratios was analyzed with the Wilcoxon signed rank test. MR findings were correlated with histopathologic findings, including those of electron microscopy.Twenty-four hours after USPIO administration in the high-dose group, susceptibility effects were present in abscess periphery on postcontrast T2*-weighted images (P=.04), and SI enhancement was noted on postcontrast T1-weighted images within both abscess wall and abscess center (P=.04 for both). In the low-dose group, SI enhancement was noted in entire abscess on T1-weighted postcontrast images (P=.03). Neither significant SI loss (P=.09) nor susceptibility effects were detected in periphery or center of any abscess on postcontrast T2*-weighted images. There was no obvious difference in total amount of macrophages among the groups, but there was a clear difference with regard to individual iron content of iron-positive macrophages between the USPIO dose groups.At 1.5 T, SI characteristics of abscesses on T1- and T2*-weighted images obtained 24 hours after USPIO injection strongly depend on administered dose of the contrast agent. At low doses, T1 effects were stronger than T2* effects.

Abstract

To evaluate intravenously administered ultrasmall superparamagnetic iron oxide (USPIO) as a marker of macrophage activity in an experimental rabbit model of antigen-induced arthritis.Unilateral arthritis was induced by means of intraarticular injection of methylated bovine serum albumin in 10 knees of 10 rabbits that had been presensitized to the same antigen. The contralateral knees in these rabbits, as well as six knees in three other rabbits, served as controls. After onset of arthritis, all knees were imaged prior to and 24 hours after administration of USPIO. The magnetic resonance (MR) imaging protocol included T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo, and short inversion time inversion-recovery sequences. Images were analyzed quantitatively and qualitatively with regard to signal characteristics and pattern. MR findings were correlated with histopathologic findings. Wilcoxon signed rank test was used to compare results of signal-to-noise ratio calculations before and after USPIO administration.All knees with intraarticular injection of antigen suspension developed unilateral arthritis, whereas no signs of arthritis occurred in the control knees. On USPIO-enhanced images obtained 24 hours after contrast agent administration, significant T1 (P =.03) and more predominantly T2* (P =.02) and T2 effects (P =.01) were evident in the synovium of all 10 arthritic knees, which reflected USPIO uptake by macrophages in the synovial tissue. To a lesser extent, T2* effects were present also within the joint effusion (P =.01). No significant changes in signal characteristics were detected in the 10 nonarthritic knees in the antigen-injected group or the six knees in the control group (P =.06-.91). Histologic examination confirmed uptake of iron in the macrophages of arthritic knees. Changes in MR signal characteristics within the arthritic synovium and synovial effusion were visually detectable after intravenous administration of USPIO.MR imaging at 1.5 T can depict USPIO uptake in phagocytic-active macrophages in an antigen-induced arthritis animal model.

Abstract

To probe the potential and pitfalls of contrast medium first-pass skeletal muscle perfusion imaging under reproducible stress conditions.Magnetic resonance (MR) signal dynamics in calf muscle and lower-leg arteries of 20 healthy volunteers were analyzed under postarterial occlusion reactive hyperemia and concurrent contrast medium first pass, using a saturation recovery spoiled gradient-echo type sequence without heartbeat synchronization. The signal vs. time curves were analyzed descriptively and by two-compartment deconvolution analysis.Highly significant changes in calf muscle signal dynamics in the hyperemic leg vs. those in the contralateral leg at rest were found in phenomenological and deconvolution analysis. Although a distortion of the arterial signal derived input function by inflow effects was found to cause large variations of the deconvolution results, the magnitude of the observed effects suggested a potential for immediate visual detection of areas with reduced tissue perfusion.The first-pass approach appeared promising for visual evaluation. However, a disentanglement of inflow and contrast medium-induced effects on arterial signal intensity was deemed a prerequisite for input function-based numerical assessment.

Abstract

To evaluate position related changes of the menisci in asymptomatic volunteers based on MR imaging of the knee in different positions.Twenty-two knees from 22 asymptomatic volunteers with no history of knee injury and no evidence of meniscal tears were examined with a 0.5-T open-configuration MR system. Sagittal and coronal images were obtained with the knee supine in neutral, supine in 90-degree flexion with external and internal rotation, as well as in upright weight-bearing positions. The position of the menisci from the outer inferior edge of the meniscus to the outermost edge of the articular cartilage of the tibial plateau was measured, and meniscal movement was calculated. The Wilcoxon signed-rank test was used for statistical analysis.Meniscal movement in the sagittal plane was greatest in the anterior horn of the medial meniscus upon position change from supine neutral to supine in 90-degree flexion with external rotation (mean, 10.5 millimeters). The least meniscal movement was observed in the anterior horn of the lateral meniscus when changing from the supine neutral to the upright knee position (mean, 0.6 millimeters). Meniscal protrusion (ie, protrusion of any part of the meniscus beyond the tibial plateau) was noted most frequently for the anterior horn of the medial meniscus (14/22 instances; 63.6%) in the sagittal plane with the knee in neutral position (mean, 2.6 millimeters, range, 1.8-2.8 millimeters). In the coronal plane, medial meniscal protrusion was most frequently present in the upright weight-bearing position (11/22 instances (50%; mean, 2 millimeters; range, 1.2-2.6 millimeters).: Meniscal movement is most prominent in the anterior horn of the medial meniscus with the knee in the supine position in 90-degree flexion with external rotation. Meniscal protrusion is more frequently present in the medial meniscus and averaged less than 3 millimeters in normal volunteers in either the sagittal or coronal MR imaging plane.

Abstract

To evaluate contrast-enhanced MR angiography for the distinction between perigastric and submucosal fundal varices.Nineteen consecutive patients with clinically suspected fundal varices underwent contrast-enhanced MR angiography and endoscopic ultrasound (EUS) within one week. Diagnostic confidence for the detection of perigastric and submucosal fundal varices was compared between MR angiography (two radiologists) and EUS (one gastroenterologist), and the agreement of size and location was evaluated.Both MR angiography and EUS detected perigastric varices in all 19 patients and submucosal fundal varices in 14 of the 19 patients. The interobserver reliability of MR angiography was good for measuring the variceal diameter (kappa = 0.76) and excellent for localizing the varices (kappa = 1.0). EUS and MR angiography agreed in 12 of 14 patients (86 %) in determining variceal diameter and location.Contrast-enhanced MR angiography is comparable to endoscopic ultrasound in the detection and characterization of gastric fundal varices.

Abstract

The purpose of this study was to assess accuracy and reliability of a volumetric analysis of abdominal aneurysms on the basis of multidetector row computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) with a commercially available automated vessel analysis software program.Twenty patients with abdominal aortic aneurysms underwent preoperative CTA and MRA before endovascular repair. Postdeployment CTA was performed in 15 of these 20 patients (75%). All preoperative CTA and MRA and postdeployment CTA data sets were analyzed with an automated software tool. The length of the stent grafts on postdeployment CTA was measured and compared with the true length of the primary component. Two readers independently evaluated 13 vessel parameters on preoperative CTA and MRA, which are considered to be important in planning stent graft deployment.With the automated analysis software tool, all measurements could be performed on either CTA or MRA data sets. There was no statistically significant difference between postdeployment measurements of stent graft length on CTA and the true dimensions of the implanted stent grafts. Interobserver agreement for all of the measurements with either CTA or MRA was good to excellent (interclass coefficient, 0.71 to 0.99) with only minimal mean differences of measured dimensions between both readers (range, -2.0 to +2.3 mm, Bland-Altman). Intermodality agreement between CTA and MRA was good to excellent (interclass coefficient, 0.62 to 0.98) with small mean differences of measured dimensions between both methods (range, -4.1 to +2.1 mm, Bland-Altman).Volumetric measurement with an automated analysis software tool allows a fast, precise, and reliable noninvasive preoperative determination of all aortic dimensions on the basis of either CTA or MRA data sets.

Abstract

With increasing life span osteoporosis becomes a more recognized problem in patients with cystic fibrosis (CF). The aim of this cross-sectional study in 75 adult patients with CF (mean age 25.3 years) was to assess the prevalence of low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and, for the first time, by quantitative ultrasound (QUS), and to identify predicting factors.Bone status was assessed at the lumbar spine (L2-L4) and the femoral neck by DEXA, and at the calcaneus by QUS (stiffness index). These data were correlated with a variety of clinical and anthropomorphic variables. Biochemical markers of bone turnover such as osteocalcin, bone-specific alkaline phosphatase, crosslinks in urine, 25-hydroxy vitamin D (25-OH vitamin D), parathyroid hormone, calcium and free testosterone were determined by standard assays.The mean BMD T score (+/-s.e.m.) was -1.4+/-0.17 at the lumbar spine, and -0.54+/-0.16 at the femoral neck. The mean T score of the calcaneal stiffness index was -0.83+/-0.19. Based on a lumbar spine T score

Abstract

Metastases of the adrenal gland are a frequent finding in patients with malignant tumors like bronchogenic carcinoma or breast cancer. Only limited and conflicting data on adrenocortical function in these patients are available.Cross-sectional study.We investigated the impact of adrenal macrometastases on adrenocortical function in a series of 28 tumor patients using the ACTH(1-24) stimulation test and dexamethasone suppression test. Seven normal controls (Con), eleven patients without adrenal metastases (No Met), eight patients with unilateral (Uni Met) and nine patients with bilateral adrenal metastases (Bil Met) were investigated.The prevalence of adrenal insufficiency was low in our study population, with only two of nine patients with bilateral metastases having subclinical adrenocortical insufficiency. In the remaining patients with uni- or bilateral metastases, baseline and stimulated cortisol concentrations were higher than in controls and cancer patients without metastases (baseline cortisol (in nmol/l): Con: 307+/-33.2 vs Uni Met: 440+/-53.5, and Bil Met: 637.6+/-92.1, P=0.04 by ANOVA; cortisol 60 min after ACTH(1-24): Con: 794.6+/-41.2 vs Uni Met: 990.8+/-92.9, and Bil Met: 1151.4+/-155.5, P=0.03 by ANOVA). Simultaneously, baseline and stimulated serum aldosterone concentrations were significantly blunted in the tumor groups.Adrenal insufficiency is infrequent and develops only in patients with bilateral metastases. However, the majority of patients have activation of the hypothalamic-pituitary-adrenal axis despite adrenal metastases with strongly elevated cortisol concentrations.

Abstract

Perforation, a severe complication of necrotizing enterocolitis (NEC), has a high mortality rate. Recently, we presented a new technique for evaluation of NEC: measuring the CT attenuation coefficient of urine after oral administration of iohexol. We present three cases of neonates with NEC who demonstrated serial increases in urine CT attenuation coefficients, all of whom subsequently deteriorated clinically and radiographically. Surgery in all three cases confirmed severe necrosis and/or perforation. These three cases suggest that the CT attenuation coefficient of urine after oral administration of iohexol may be a more sensitive indicator of NEC severity, progression, and perforation than clinical evaluation and radiography. More investigation is necessary, but eventually, this noninvasive technique may be able to decrease morbidity and mortality by predicting the need for surgical intervention or more aggressive medical management of NEC before perforation occurs.

Abstract

Meconium peritonitis is a chemical peritonitis which occurs following bowel perforation during fetal life. It is generally looked upon as benign, resulting in no long-term sequelae. We present a case of a newborn infant with meconium peritonitis who developed infarcts in several organs. At autopsy the infarcts proved to be caused by emboli as a result of intravascular dissemination of meconium. To our knowledge, this is the first reported case of systemic spread of meconium peritonitis in the literature and suggests that meconium peritonitis may have more serious implications than generally thought.